Project 2: Cardiometabolic Disease in an Aging South African Cohort?Abstract Cardiometabolic disease (CMD) has become the leading cause of death globally as a result of epidemiologic, social, and economic transitions. Furthermore, advances in care have moved the burden of CMD onto older adults, who tend to have comorbidities and may be frail, which affects both prognosis and treatment decisions. As part of the Health and Aging in Africa: Longitudinal Studies of an INDEPTH Community (HAALSI) Program, Project 2 will assess the trajectories of traditional and novel risk factors for CMD and test whether easily identified and modifiable risk factors predict future CMD morbidity and both CMD and non-CMD mortality in an African population ?40 years. Data will be collected over six years with baseline studies completed in 2015/16 and two further waves, three years apart. Effective follow-up of cohort participants with collection of self-reported health status linked to actual clinic use, along with testing of established and novel biomarkers, will lead to a detailed understanding of the complex biologic, behavioral, demographic, and socioeconomic factors that result in increasing CMD morbidity and mortality. Project 2 is linked to Project 1 through a study of associations of CMD with cognitive impairment and dementia; Project 3 through the study of HIV/AIDS and antiretroviral therapy; Project 4 through its investigation of the impacts of salt legislation; and Project 5 through its focus on multimorbidity and frailty. We have additional genetic input into CMD risk factors through an ongoing collaboration with the Human Heredity & Health in Africa (H3Africa) project/Africa Wits-INDEPTH Partnership for the Genomic Study of Body Composition and Cardiometabolic Disease Risk (AWI-Gen). Reliable data on baseline levels of chronic CMD-related conditions, including cardiovascular diseases, stroke and diabetes in older populations are extremely limited in rural South Africa, yet understanding the rate of change in CMD is critical for planning health and social policy. Our long-term goal is to use these data to inform planning of health and social services with capacity to identify and target high-risk middle age and older persons who may benefit from simple interventions to reduce CMD morbidity and mortality. The specific aims are to: AIM 1: Evaluate the scale and trajectory of CMD in the HAALSI cohort, including the prevalence, incidence, and mortality of key conditions and their risk factors. AIM 2: Evaluate the effects of critical social determinants, in particular migration and socioeconomic disadvantage, on CMD risk. AIM 3: Develop models for identifying individuals at high risk for CMD and generate projections of future population-level CMD burden. AIM 4: Assess the evolving impact of South Africa's 2013 salt legislation (in effect from 2016) on CMD risk.